Taxanes hypersensitivity is not a risk factor for severe reactions to SARS-CoV-2 vaccines.

Summary: Background. Hypersensitivity reactions (HSR) to taxanes have been related to a complement activation by their excipients, polyoxyethylated castor oil and Polysorbate 80, structurally related to those of SARS-CoV-2 vaccines. The aim of this study was to verify the presence of a higher risk of HSR to SARS-CoV-2 vaccines in patients with history of HSR to taxanes. Methods. Patients with history of HSR to taxanes were evaluated before the vaccination in our center and underwent skin tests for PEG and Polysorbate 80 (PandP). Some patients completed the vaccination course in other centers without prior PandP skin tests because they had not manifested taxanes hypersensitivity before vaccination, or because those tests were not available. Results. 50 patients were evaluated. 100% of patients with history of hypersensitivity to taxanes completed the vaccine course with no cases of anaphylaxis. 33 underwent skin tests for PandP before the vaccination and no correlation was found between the positivity of PandP and taxanes skin tests (p = 0.538). 7 patients developed mild symptoms during skin tests and vaccination, similar but weaker than those suffered at the time of the taxane infusion, independently from the results of skin tests. Conclusions. In our cohort patients with history of reaction to taxanes were not at higher risk to develop anaphylaxis to SARS-CoV-2 vaccines. However, a common non-IgE mediated mechanism behind those HSRs cannot be completely excluded. This can only account for mild and harmless symptoms in case of SARS-CoV-2 vaccines. However, prudence is still recommended in these patients.

Predictors of response to omalizumab and relapse in chronic spontaneous urticaria: a study of 470 patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as spontaneous occurrence of wheals and/or angioedema for ≥6 weeks. Omalizumab is a monoclonal anti-IgE antibody effective in refractory CSU, but its mechanism of action and markers predictive of response remain not completely defined. OBJECTIVES: To correlate baseline levels of two proposed biomarkers, total IgE (bIgE) and d-dimer (bd-dimer), and clinical parameters to omalizumab response and to relapses after drug withdrawal. METHODS: In this retrospective Italian multicentre study, clinical data were collected in 470 CSU patients, and bIgE and bd-dimer were measured in 340 and 342 patients, respectively. Disease activity was determined by Urticaria Activity Score 7 (UAS7) at week 1 and 12 after omalizumab starting. Relapses were evaluated during a 2- and 3-month interval after a first and a second course of treatment, respectively. RESULTS: bIgE correlated to a good response to omalizumab since levels were significantly higher in responders than non-responders (P = 0.0002). Conversely, bd-dimer did not correlate to response. There was no correlation between both bIgE and d-dimer and either first or second relapse. Disease duration was significantly longer in patients who experienced either first or second relapse (P < 0.0001 and P = 0.0105, respectively), while baseline UAS7 correlated only to first relapse (P = 0.0023). CONCLUSIONS: Our study confirms bIgE as a reliable biomarker predicting response to omalizumab in CSU, while it does not support the usefulness of bd-dimer unlike previous findings. CSU duration before omalizumab and baseline UAS7 may be clinical markers of relapse risk.

Bilastine safety in drivers who need antihistamines: new evidence from high-speed simulator driving test on allergic patients.

OBJECTIVE: Bilastine is a highly selective, non-sedating antihistamine, indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Available data suggest that bilastine interferes neither with driving ability nor with flying-related performance. However, no data are available on the effect of bilastine on the driving ability in extreme conditions. Here we analyzed the effect of 7 days treatment with 20 mg bilastine in patients with allergic rhinitis and/or chronic urticaria, on psychophysical performance assessed by the Formula One (F1) high-speed simulator-driving test. PATIENTS AND METHODS: This study is a phase IV, interventional, prospective, mono-centric, single arm, open-label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic urticaria, able to perform a preliminary driving test on F1 simulator were considered (V-1). First, the patients had a screening visit to assess their eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment and Visit 2 (V2), at the end of bilastine treatment. The primary variable parameter was the ability to maintain the vehicle in a central position at different speeds (50, 150, and 250 km/h). RESULTS: Bilastine had a good safety profile and was well tolerated in terms of adverse events, laboratory parameters and vital signs. Bilastine did not have any negative effect on the ability to maintain the requested path, a constant speed as well as on attention and reactivity levels, even in extreme driving conditions. CONCLUSIONS: This study is the first done in patients with allergic rhinitis and/or chronic urticaria using a F1-high speed simulator-driving test evaluating subjects' performance under bilastine treatment.

Pazopanib and sunitinib trigger autophagic and non-autophagic death of bladder tumour cells.

BACKGROUND: Tyrosine kinase inhibitors (TKI) such as sunitinib and pazopanib display their efficacy in a variety of solid tumours. However, their use in therapy is limited by the lack of evidence about the ability to induce cell death in cancer cells. Our aim was to evaluate cytotoxic effects induced by sunitinib and pazopanib in 5637 and J82 bladder cancer cell lines. METHODS: Cell viability was tested by MTT assay. Autophagy was evaluated by western blot using anti-LC3 and anti-p62 antibodies, acridine orange staining and FACS analysis. Oxygen radical generation and necrosis were determined by FACS analysis using DCFDA and PI staining. Cathepsin B activation was evaluated by western blot and fluorogenic Z-Arg-Arg-AMC peptide. Finally, gene expression was performed using RT-PCR Profiler array. RESULTS: We found that sunitinib treatment for 24 h triggers incomplete autophagy, impairs cathepsin B activation and stimulates a lysosomal-dependent necrosis. By contrast, treatment for 48 h with pazopanib induces cathepsin B activation and autophagic cell death, markedly reversed by CA074-Me and 3-MA, cathepsin B and autophagic inhibitors, respectively. Finally, pazopanib upregulates the α-glucosidase and downregulates the TP73 mRNA expression. CONCLUSION: Our results showing distinct cell death mechanisms activated by different TKIs, provide the biological basis for novel molecularly targeted approaches.

New limits on Planck scale Lorentz violation in QED.

Constraints on possible Lorentz symmetry violation (LV) of order E/M(Planck) for electrons and photons in the framework of effective field theory (EFT) are discussed. Using (i) the report of polarized MeV emission from GRB021206 and (ii) the absence of vacuum Cerenkov radiation from synchrotron electrons in the Crab Nebula, we improve previous bounds by 10(-10) and 10(-2), respectively. We also show that the LV parameters for positrons and electrons are different, discuss electron helicity decay, and investigate how prior constraints are modified by the relations between LV parameters implied by EFT.

A strong astrophysical constraint on the violation of special relativity by quantum gravity.

Special relativity asserts that physical phenomena appear the same to all unaccelerated observers. This is called Lorentz symmetry and relates long wavelengths to short ones: if the symmetry is exact it implies that space-time must look the same at all length scales. Several approaches to quantum gravity, however, suggest that there may be a microscopic structure of space-time that leads to a violation of Lorentz symmetry. This might arise because of the discreteness or non-commutivity of space-time, or through the action of extra dimensions. Here we determine a very strong constraint on a type of Lorentz violation that produces a maximum electron speed less than the speed of light. We use the observation of 100-MeV synchrotron radiation from the Crab nebula to improve the previous limit by a factor of 40 million, ruling out this type of Lorentz violation, and thereby providing an important constraint on theories of quantum gravity.